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Haematologica. 2019 Jun;104(6):1268-1276. doi: 10.3324/haematol.2018.205666. Epub 2018 Dec 6.

Generation of anti-idiotypic antibodies to detect anti-spacer antibody idiotopes in acute thrombotic thrombocytopenic purpura patients.

Author information

1
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Belgium.
2
Service d'Hématologie Biologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, France.
3
EA3518, Institut Universitaire d'Hématologie Saint-Louis, Université Paris Diderot, France.
4
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Italy.
5
Department of Pathophysiology and Transplantation, Fondazione Luigi Villa, Milan, Italy.
6
Department of Molecular and Cellular Hemostasis, Sanquin-AMC Landsteiner Laboratory, Amsterdam, the Netherlands.
7
Department of Internal Medicine, Meander Medical Center, Amersfoort, the Netherlands.
8
Sorbonne Universités, Service d'Hématologie et Centre de Référence des Microangiopathies Thrombotiques (CNR-MAT), Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, France.
9
Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Belgium Karen.Vanhoorelbeke@kuleuven.be.

Abstract

In autoantibody-mediated autoimmune diseases, autoantibody profiling allows patients to be stratified and links autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed to develop a new type of autoantibody profiling assay for iTTP based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer idiotopes from 151 acute iTTP plasma samples. We next deciphered these anti-spacer idiotope profiles in iTTP patients and investigated whether these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding; 35%, 24% and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles provided a new insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 idiotopes in iTTP patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow idiotope profiles of clinical, prognostic value to be identified.

PMID:
30523052
DOI:
10.3324/haematol.2018.205666
Free PMC Article

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